Beta cells, the insulin-producing cells of the pancreas, comprise more than 70% of the cell population found in discrete collections of cells in the pancreas which are known as islets of Langerhans. Some major effects of insulin are to increase the uptake of glucose by various tissues including muscle and fat and to decrease glucose output by the liver. Either absolute or relative insulin deficiency impairs glucose uptake and increases hepatic glucose output, thereby resulting in the abnormally high blood glucose concentrations characteristic of diabetes mellitus.
Insulin release from pancreatic islets is controlled by a combination of factors, including the concentration of glucose and other nutrients in the blood, gastrointestinal hormones and neuronal stimuli. In humans, glucose is the principal stimulus for insulin secretion from beta cells. However, other fuels such as amino acids and fatty acids also promote secretion.
Diabetes is generally characterized by an elevated concentration of glucose in the blood and urine. Insulin is administered to a diabetic patient in an effort to control or regulate the concentration of glucose and other nutrients in the blood. The objective of this regimen is to maintain glucose levels close to normal. One possible reason for the failure of this treatment to prevent the complications associated with diabetes is that daily insulin injections do not mimic the rapid insulin secretory responses of normal islets to physiological demand. Consequently, there has been a great deal of interest in developing a treatment for diabetics which would make it possible to maintain normal blood glucose levels at all times, an objective extremely difficult or impossible to achieve by insulin injections, diet and exercise.
Attempts have been made to produce an electromechanical artificial pancreas system comprised of, a glucose sensor, an information processor and an insulin pump to mimic physiological response patterns for insulin release. Thus far, this approach has not been effective.
Another approach to treating diabetes is replacement of the malfunctioning organ by transplantation of normal pancreatic tissue. However, transplantation of pancreatic tissue has met with limited success due to problems of tissue typing, donor availability and immune rejection.
To address these problems, researchers have focused on creating a hybrid artificial pancreas which mimics the organ's physiological response to glucose levels. Artificial pancreatic devices containing live islets have been designed to avoid immune rejection. These devices contain a semipermeable membrane which separates the transplanted islets from immunoreactive cells and molecules.
Matsumura describes an artificial pancreas device which includes a semipermeable membrane on one side of which once-dispersed live pancreatic islets are placed. (U.S. Pat. No. 3,827,565).
Sun et al. (U.S. Pat. No. 4,323,457 (1982)) describe another artificial pancreatic device which is a container means through which a hollow fiber of 500 .mu.m diameter is passed. The container holds pancreatic islets and the fiber is described as having a porosity which allows for passage of substances of molecular weight less than 100,000 Daltons.
Chick et al.: (U.S. Pat. Nos. 4,242,459 and 4,242,460 (1980)) describe a cell culture device having a generally circular fluid-tight cavity and a semipermeable tube wrapped about itself to form coils. Another cell culture device comprises a housing and a stationary spool about which a semipermeable tube is wrapped to form coils.
None of the presently-available artificial pancreatic devices solve the problems associated with diabetes and with implantation of an artificial device into an individual. Thus, there is a need for a pancreatic device containing viable islets of Langerhans which can be implanted into a diabetic individual and be effective in controlling blood glucose levels in such a way as to mimic normal physiological response to changing blood glucose concentrations. Although parent application U.S. Ser. No. 07/398,739 discloses one such device, that device does not provide for replacement of islets during in vivo use. Thus, there is a need for a pancreatic device in which islets can be removed from the device and replaced with fresh islets at various times during use, for example upon a drop in insulin output.